ACP-105 is one of the least studied substances sold under the SARM label. It is written about as a "soft" modulator for "dry mass", but only a few preclinical works are devoted to it in the peer-reviewed scientific literature. The editors explain what this molecule is, how it interacts with the androgen receptor, and where the facts end.
Origin and chemical nature of ACP-105
ACP-105 was created in the American pharmaceutical company ACADIA Pharmaceuticals within the scope of the search program for new non-steroidal androgen receptor modulators. The results of this program are described in an article by Schlienger et al published in the Journal of Medicinal Chemistry in 2009. The work is devoted to the synthesis of a series of compounds, the analysis of the "structure-activity" relationship and the primary pharmacological characteristics of the most promising of them.
According to the chemical structure, ACP-105 is not similar either to steroids or to the most famous SARM groups of arylpropionamides (ostarine, andarine, S23). The basis of the molecule is a substituted benzonitrile attached to a bicyclic nitrogen-containing fragment of the tropane type. The nitrile group and the halogen in the aromatic ring are characteristic elements of many nonsteroidal ligands of the androgen receptor.
The nonsteroidal structure has several implications. First, ACP-105 is not an aromatase substrate and does not convert to estrogens like testosterone. Secondly, it does not interact with 5-alpha-reductase and does not form analogues of dihydrotestosterone. Thirdly, its metabolism and interactions with other receptors differ from classical androgens and are much less well studied.
The name "ACP-105" is a laboratory code, not an international non-proprietary name. The compound did not receive a trade name, was not registered as a medicinal product and, as far as is known from open sources, did not reach the stage of published clinical trials.
Androgen receptor and the idea of selectivity
Androgen receptor is an intracellular protein that, after binding with the hormone, moves into the cell nucleus and regulates the activity of hundreds of genes. The same receptor is present in muscles, bones, prostate, skin, hair follicles, brain and liver. Therefore, classical androgens affect all these tissues simultaneously.
The idea behind SARMs is to find ligands that change the conformation of the receptor so that it interacts differently with coregulatory proteins (coactivators and corepressors) in different tissues. As a result, the compound may act as a full agonist in muscle, but as a weak agonist or even antagonist in the prostate (Narayanan et al., 2018).
The selectivity of SARMs in preclinical work is usually evaluated in castrated rats: comparing how the compound restores the mass of the levator ani muscle (an anabolic marker) and the mass of the prostate and seminal vesicles (androgenic markers). ACP-105 is also characterized according to this principle.
It should be emphasized that this model is a molecular screening tool, not proof of clinical benefit. It does not answer questions about human strength or endurance, effects on the heart, lipids or liver, or long-term safety.
Partial agonism: what it means
One of the features of ACP-105 that the authors emphasized is partial agonism at the androgen receptor. A full agonist, such as testosterone or dihydrotestosterone, is able to activate the receptor to a maximal level. A partial agonist, even with full receptor occupancy, produces only a fraction of this maximal response.
In cellular tests, ACP-105 exhibited exactly this profile. Theoretically, this can be useful: a partial agonist is able to support anabolic signals in conditions of androgen deficiency, but with a high level of own androgens, it can partially compete with them. Such a "buffer" effect makes the behavior of the compound dependent on the hormonal background of the body.
In practice, this means even greater unpredictability. The effect of ACP-105 in a person with normal testosterone levels can be radically different from the effect in the castrated rat on which it was studied. There are no controlled data on this situation.
- Full agonist: maximal receptor activation (testosterone, DHT, most steroids).
- Partial agonist: limited maximal activation; the effect depends on the presence of other ligands.
- Antagonist: blocks the receptor without activation (eg, antiandrogens bicalutamide, flutamide).
Partial agonism does not mean "weakness" in the sense of safety. Partial activation of receptors may be sufficient to suppress the hypothalamic-pituitary axis, so this property is not an argument in favor of the absence of hormonal side effects.
What is known about pharmacokinetics and metabolism
Published data on the pharmacokinetics of ACP-105 are limited to preclinical models. In the work of Schlienger et al. the compound was evaluated, in particular, for bioavailability when administered orally to animals, which was one of the conditions for selecting a candidate for further research.
Most is known about the metabolism of ACP-105 from anti-doping studies. Human and equine control laboratories have studied the compound's metabolites in vitro (in liver microsomes) and in vivo in animals to find markers by which it can be detected in urine and blood. The main ways of biotransformation are oxidation and conjugation.
| Parameter | What is known | Data source |
|---|---|---|
| Compound type | Nonsteroidal partial AR agonist | Medicinal chemistry, cell tests |
| Tissue selectivity | Anabolic effect is more pronounced than androgenic | Castrated rats |
| Oral activity | Shown in animals | Preclinical data |
| Half-life in humans | Not established | There are no clinical data |
| Metabolites | Described for doping control purposes | Anti-doping research |
The "half-life" and "optimal dose" numbers floating around the forums have no support in human studies. They are either ported over from other SARMs or made up by vendors for marketing convenience.
The lack of pharmacokinetic data in humans is not a technical trifle. It is these data that determine whether the substance accumulates, how it interacts with other drugs, and how long it remains in the body after the last dose.
Place of ACP-105 among other SARMs and status
Two groups can be distinguished among the SARMs that are being talked about in the sports environment today. The first includes compounds that have undergone at least early clinical trials: enobosarm (ostarine), LGD-4033 (ligandrol). The second is compounds known mainly from preclinical work, such as S23 or ACP-105.
ACP-105 belongs to the second group. In addition to the original Medicinal Chemistry article, it was used in an experimental study in a mouse model of Alzheimer's disease (George et al., 2013) examining the effects of androgen and estrogen receptor modulators on behavior and beta-amyloid levels. This is basic science, not the development of a muscle-building tool.
In sports, ACP-105, like all SARMs, is prohibited by the World Anti-Doping Agency in class S1.2 "Other anabolic agents". As a medicinal product, it is not registered anywhere, so it is sold under the guise of "reagents" or "additives" outside the quality control system.
For the consumer, this means a double uncertainty: it is not known how the compound affects humans, and it is not known whether it is even present in a particular product. Independent analyzes of marketed SARMs show that the composition often does not match the label (Van Wagoner et al., 2017).
Editorial conclusions
ACP-105 is a nonsteroidal partial androgen receptor agonist synthesized as a SARM candidate and characterized only in preclinical models.
Its tissue selectivity is shown in castrated rats and partial agonism in cell tests. These data do not automatically transfer to a person and do not say anything about long-term safety.
The lack of clinical trials, registration, and quality control makes ACP-105 a substance with an unknown risk profile that is prohibited in sports.
Our materials "ACP-105: what clinical and preclinical studies show", "Side effects of ACP-105" and "Legal status of ACP-105 and the WADA ban" will help to continue the topic.
List of used literature
- Schlienger N, Lund BW, Pawlas J, et al. Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators. J Med Chem. 2009;52(22):7186â7191.
- George S, Petit GH, Gouras GK, Brundin P, Olsson R. Nonsteroidal selective androgen receptor modulators and selective estrogen receptor β agonists moderate cognitive deficits and amyloid-β levels in a mouse model of Alzheimer's disease. ACS Chem Neurosci. 2013;4(12):1537â1548.
- Narayanan R, Coss CC, Dalton JT. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. 2018;465:134â142.
- Thevis M, Schänzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2018;464:34â45.
- Van Wagoner RM, Eichner A, Bhasin S, Deuster PA, Eichner D. Chemical composition and labeling of substances marketed as selective androgen receptor modulators and sold via the internet. JAMA. 2017;318(20):2004â2010.
- World Anti-Doping Agency. Prohibited List. Montreal: WADA; Ñинна ÑедакÑÑÑ.
